The invention relates to a microdispenser for dispensing a liquid sample in a dispensing device and also to an associated operating method.
Microdispensers are known for example from WO 99/30168 and are used inter alia for biological or chemical purposes in order to dispense small volumes of liquid in a controlled manner in the form of microdroplets. One example of this is the production of miniaturized DNA arrays for genetic engineering uses, wherein a high clone density is achieved by means of a small droplet size, for which piezoelectrically operated microdispensers are particularly suitable. The known microdispensers consist of a glass capillary for holding the sample liquid to be dispensed, the glass capillary having a nozzle for dispensing the microdroplets and a flexible supply line for filling it with the sample liquid. The discharging of the microdroplets from the glass capillary in the known microdispensers is brought about by means of a piezo actuator, which surrounds the glass capillary in the manner of a sleeve in the region of a narrowing and expands or compresses the glass capillary in the radial and/or longitudinal direction in the event of electrical actuation, as a result of which a shock wave is generated in the glass capillary which, after reflection at the narrowing of the glass capillary, discharges microdroplets out of the glass capillary through the nozzle.
One disadvantage of the known microdispensers described above is the fact that filling and operation of the glass capillary via a flexible hose can lead to contamination since the plastic hoses which are typically used, may form biofilms. Sterile handling of the transition points between the plastic hose and the glass capillary is particularly problematic, since this area contains corners and edges in which it is possible for contaminations (e.g. biofilms) to be deposited, in which bacteria, viruses, fungi and yeasts may in turn settle. This problem of contamination when filling the glass capillaries is particularly disadvantageous when the microdispensers are used in the diagnostics sector, since the contamination may then lead to faulty products and incorrect diagnoses.
When handling the known microdispensers, the problem generally exists that the microdispensers are subjected to operating cycles which consist of uptake by suction (filling), dispensing and subsequent rinsing. These operating cycles are repeated with the same microdispenser for the next sample or for a number of samples and may lead to so-called cross-contamination, and take up a large amount of time.
Furthermore, it must be noted with regard to the prior art that, in the case of so-called high throughput screening, the substances to be tested are usually stored dissolved in DMSO (dimethyl sulphoxide) in microtiter plates, wherein the microtiter plates containing a plurality of samples are deep-frozen. In order to remove a single sample, the entire microtiter plate along with all the samples located therein then has to be thawed, whereby moisture from the air can condense into the samples, which leads to impairment of the samples.
Furthermore, U.S. Pat. No. 6,191,946 discloses a microdispenser which is filled, cleaned and emptied via the nozzle. Moreover, the microdispenser in this case has a sample channel which is accessible from outside and therefore cannot be stored or transported in the filled state.
WO 97/44 134 A1 also discloses a microdispenser, which is filled from the front via the nozzle and therefore has the same problems as the known microdispenser described above, i.e. the microdispenser cannot be stored or transported in the filled state.
Patent application EP 0 469 444 A1 discloses a disposable (single-use) nozzle unit which contains the analysis liquid in pre-filled form. However, here the analysis liquid is discharged according to the bubble-jet technique, which heats up the analysis liquid and therefore is not suitable for the microdispenser according to the invention since, with the small dimensions of the microdispenser according to the invention, the heating that is required in the bubble-jet method in order to produce vapor bubbles would damage, i.e. denaturize, the biological samples in the sample liquid.
U.S. Pat. No. 6,296,811 B1 and U.S. Pat. No. 6,866,825 disclose a microdispenser in which the filling of the microdispenser with the sample liquid to be dispensed takes place via lines, which is associated with the problems of contamination described above.
Furthermore, DE 26 53 051 A1 and DE 101 06 362 A1 disclose pipettes for taking blood, which also allow storage. However, these are not microdispensers within the meaning according to the invention. The same applies in respect of the pre-filled pipettes known from WO 02/42175 A1 and U.S. Pat. No. 6,457,612.
Moreover, U.S. Pat. No. 6,232,129 B1 discloses a conventional piezoelectric pipetting device for transferring droplets of samples between two containers. However, these pipetting devices do not allow long-term storage in the filled state.
Finally, U.S. Pat. No. 4,528,579, U.S. Pat. No. 4,418,354 and U.S. Pat. No. 4,528,578 disclose microdispensers for inkjet printers, which as such are not suitable for dispensing biological samples.
The task of the invention is therefore to improve the known microdispensers in such a way that as far as possible no contamination or impurities occur.